Current investigations involve the mechanisms by which activation of the complement system results in the destruction of connective tissue. Immunoglobulins reactive with cell surface antigens in bone initiate complement activation via either the classical or alternative pathway with resultant destruction of bone in organ cultures. This pathological event is mediated by prostaglandins synthesized by the bone. Osteoclasts are involved in bone resorption and recent studies have demonstrated that a cell of similar origin, the macrophage, can be stimulated by antibody and complement to synthesize prostaglandins. One mechanism by which complement exerts these effects has been shown to be the enhancement of the incorporation of the prostaglandin precursor arachidonic acid, into prostaglandins. Current studies focus on the effects of hormones on complement mediated prostaglandin systhesis, the complement components involved in this reaction and the mechanism by which prostaglandins produce the ultimate destruction of connective tissue.